This Competitive Renewal Application from the UPR-RP MBRS SCORE Program aims for continued growth in the quality and amount of biomedical research at the University of Puerto Rico-Rio Piedras. Recognizing that raising the level of achievement entails greater productivity and more emphasis on competitive research funding, the following goals have been established for this funding cycle: 1) To enhance the biomedical research competitiveness of the faculty (knowledge, skills and capabilities) by their participation in scientifically meritorious research projects and by their involvement in associated activities. 2) To provide more opportunity for qualified graduate, undergraduate and postdoctoral students to participate in biomedical research; and 3) To strengthen the institutional commitment of UPR-Rio Piedras to biomedical research. These goals will be achieved by increasing the number of competitive grant applications at the rate of one per year per investigator, increasing the number of peer reviewed publications per year per investigator from the current average of 3.8 to 4.4, increasing the number of presentations per laboratory per year from the current average of 8 to 10, and augmenting the number of investigators engaged in biomedical research at the campus. This increased focus on research productivity is expected to result in an increase in the number of qualified and productive graduate and undergraduate students involved in biomedical research. This renewal contains 16 regular and 5 pilot projects from 7 investigators from the Biology Department, 12 from Chemistry and 2 from Mathematics. These projects aim to conduct competitive biomedical research on such topics as the role of DNA recombination and repair mechanism in learning and memory processes, the location of purinergic receptors and transducers within membrane microdomains on signalling events, the molecular aspects of organ regenerations, the functional role of lipid protein interactions in the conformational transitions of the nicotinic acetyl chlorine receptor, protein inactivation and aggregation during encapsulation and release, the physical factors that affect conformational stability of proteins, the role of mGluRs in drug addiction and which specific neural connections mediate drug-induced associative learning and addictive behavior, the trans-acting factors in nonsense-mediated mRNA decay pathway related to HRP1 trans-acting factor, the mechanism of aspergillosis in human and sea fan infections, the role of E. Coli as a possible vector of gene transmission and the possibility of soil environments serving as a reservoir of pathogenic microorganisms, the photochemical transformation of mutagenic pollutants; the synthesis or development of novel guanosine analogues to create stable G-quadruplexes for the treatment of cancer, selective asymmetric reagents and catalysts for chiral drug synthesis, an enantioselective methodology for the synthesis of polypropionate antibiotics, new MRI contrast enhancing agents of DNA nanoarray chips for disease diagnosis; the discovery of novel fatty acids that could be used as the lipid component of a prodrug, natural products from octocorals for the treatment of tuberculosis, the development and use of theoretical chemical and mathematical models for the urine concentrating mechanism, simulation of the stable conformation of nanometer sized DNA, and models of genetic networks including error correction. These investigators will be supported by an administrative structure and technical personnel funded by this program.